D1/D5 dopamine receptors inhibit depotentiation at CA1 synapses via cAMP-dependent mechanism.
Recent work has shown that D1/D5 dopamine receptors can enhance long-term potentiation (LTP). We investigated whether D1/D5 receptors also affect depotentiation, the reversal of LTP by low-frequency stimulation. D1/D5 agonists greatly reduced depotentiation, an effect that was inhibited by a D1/D5 antagonist. The D1/D5 effect appears to be mediated by adenylyl cyclase (AC) and cAMP-dependent protein kinase (PKA), because it was mimicked by the AC activator forskolin and was inhibited by the AC and PKA inhibitors. In vivo studies show that dopamine is released when a reward occurs. Our results raise the possibility that the memory of events before reward might be retained selectively, because dopamine blocks their erasure.
Otmakhova
N A
NA
Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02254, USA.
Lisman
J E
JE
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004594:Electrophysiology; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D050641:Receptors, Dopamine D5; D013569:Synapses / Q000502:physiology*
D000067956:Adenylyl Cyclase Inhibitors; C493607:Drd5 protein, rat; D004791:Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases